TREATMENT OF COMPULSIVE BEHAVIOR IN EATING DISORDERS WITH INTERMITTENT KETAMINE INFUSIONS

We have previously shown that eating disorders are a compulsive behavi our disease, characterized by frequent recall of anorexic thoughts. Ev idence suggests that memory is a neocortical neuronal network, excitat ion of which involves the hippocampus, with recall occurring by re-exc itement of the same specific network. Excitement of the hippocampus by glutamate-NMDA receptors, leading to long-term potentiation (LTP), ca n be blocked by ketamine. Continuous block of LTP prevents new memory formation but does not affect previous memories. Opioid antagonists pr event loss of consciousness with ketamine but do not prevent the block of LTP. We used infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily nalmefene as opioid antagonist to treat 15 patients wi th a long history of eating disorder, all of whom were chronic and res istant to several other forms of treatment. Nine (responders) showed p rolonged remission when treated with two to nine ketamine infusions at intervals of 5 days to 3 weeks. Clinical response was associated with a significant decrease in Compulsion score: before ketamine, mean +/- SE was 44.0+/-2.5; after ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients (non-responders) the score was: before ketamine, 42.8 +/- 3.7; after ketamine, 44.8 +/- 3.1. There was no significant respo nse to at least five ketamine treatments, perhaps because the compulsi ve drive was re-established too soon after the infusion, or because th e dose of opioid antagonist, nalmefene, was too low.